S phase kinase-associated protein 2 (Skp2), an F-box protein, is required for the ubiquitination and consequent degradation of p27(kip1). Previous reports have showed that p27(kip1 )played important roles in cell cycle regulation and neurogenesis in the developing central nervous system. But the distribution and function of p27(kip1 )and Skp2 in nervous system lesion and regeneration remains unclear. In this study, we observed that they were expressed mainly in both Schwann cells and axons in adult rat sciatic nerve. Sciatic nerve crush and transection resulted in a significant up-regulation of Skp2 and a down-regulation of p27(kip1). By immunochemistry, we found that in the distal stumps of transected nerve from the end to the edge, the appearance of Skp2 in the edge is coincided with the decrease in p27(kip1) levels. Changes of them were inversely correlated. Results obtained by coimmunoprecipitation and double labeling further showed their interaction in the regenerating process. Thus, these results indicate that p27(kip1 )and Skp2 likely play an important role in peripheral nerve injury and regeneration.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/s10571-007-9167-8 | DOI Listing |
Medicina (Kaunas)
July 2024
Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy.
Aberrant upregulation of fatty acid synthase (FASN), catalyzing de novo synthesis of fatty acids, occurs in various tumor types, including human hepatocellular carcinoma (HCC). Although FASN oncogenic activity seems to reside in its pro-lipogenic function, cumulating evidence suggests that FASN's tumor-supporting role might also be metabolic-independent. : In the present study, we show that FASN inactivation by specific small interfering RNA (siRNA) promoted the downregulation of the S-phase kinase associated-protein kinase 2 (SKP2) and the consequent induction of p27 in HCC cell lines.
View Article and Find Full Text PDFCancer Cell Int
May 2024
Cell Therapy and Immunobiology Department, King Faisal Specialist Hospital & Research Centre, Riyadh, 11211, Kingdom of Saudi Arabia.
Background: PD-L1 intrinsically promotes tumor progression through multiple mechanisms, which potentially leads to resistance to anti-PD-1/PD-L1 therapies. The intrinsic effect of PD-L1 on breast cancer (BC) cell proliferation has not been fully elucidated.
Methods: we used proteomics, gene expression knockdown (KD), quantitative immunofluorescence (qIF), western blots, functional assays including colony-forming assay (CFA) and real-time cell analyzer (RTCA), and in vivo data using immunohistochemistry in breast cancer patients.
Cell Death Dis
April 2024
College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian, 350108, P. R. China.
Soft-tissue sarcomas (STS) emerges as formidable challenges in clinics due to the complex genetic heterogeneity, high rates of local recurrence and metastasis. Exploring specific targets and biomarkers would benefit the prognosis and treatment of STS. Here, we identified RCC1, a guanine-nucleotide exchange factor for Ran, as an oncogene and a potential intervention target in STS.
View Article and Find Full Text PDFNat Commun
December 2023
Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Roma, Italy.
Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS.
View Article and Find Full Text PDFSci Rep
July 2023
Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle University, Paul O'Gorman Building, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK.
p27KIP1 (cyclin-dependent kinase inhibitor 1B, p27) is a member of the CIP/KIP family of CDK (cyclin dependent kinase) regulators that inhibit cell cycle CDKs. p27 phosphorylation by CDK1/2, signals its recruitment to the SCF (S-phase kinase associated protein 1 (SKP1)-cullin-SKP2) E3 ubiquitin ligase complex for proteasomal degradation. The nature of p27 binding to SKP2 and CKS1 was revealed by the SKP1-SKP2-CKS1-p27 phosphopeptide crystal structure.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!